Cholesterol content of serum lipoprotein fractions in children andadolescents maintained on chronic hemodialysis. fL. André, P. Gam-bert, R. Bourquard, C. Lallemant, M. Vidailhet, A. Athias, P. Padieu,and M. Pierson. Unite de Néphrologie Pédiatrique, Service de Pédia-trie B, Chu de Nancy, et Laboratoire de Biochimie Médicale, Facultéde Médecine, Ddon, France. A new method of cholesterol gas-liquidchroniatographic assay in serum lipoproteins, separated by polyacryl-amide gel electrophoresis needing only 2.5 p.1 of serum, was used toanalyze cholesterol content of serum lipoprotein fractions in childrenand adolescents maintained on chronic hemodialysis. Lipoprotein anal-ysis was performed on serum samples from nine hemodialyzed chil-dren, 6 to 17 years old, and from nine pair-matched control children.The mean serum triglyceride was significantly elevated in the hemodia-lyzed group as were the mean total cholesterol and VLDL cholesterollevels. The increase of LDL cholesterol concentration and the decreaseof HDL cholesterol concentration were not significant. Relative distri-bution of cholesterol in the individual lipoprotein classes was differentin the two groups (P < 0.001): VLDL cholesterol = 6.3 0.8% of thetotal cholesterol in the control group and 18.9 2.1% in the hemodia-lyzed group; HDL cholesterol = 28.7 2% of the total cholesterol inthe control group and only 18.9 1.4% in the hemodialyzed group.LDL cholesterol relative contents were not significantly different, butthe LDL to HDL cholesterol ratio increased from 2.41 0.29 to 3.410.23 (P < 0.05). HDL migrated faster than usual in the polyacrylamidegel, and this fraction might have undergone some qualitative changeswhich could be compatible with altered apoprotein HDL composition.These results outline the potential risk of premature atherosclerosis inunremic children on maintenance hemodialysis.

Effects of L-carnitine in hemodialyzed pediatric patients. J. L. Bacri, B.Lacour, M. f. Tete, and M. Broyer. Hopital des Enfants Malades,Paris, France. L-Carnitine effect was studied after a 4-week placeboperiod in six hemodialyzed patients, 5 to 14 years old, with hypertrigly-ceridemia. All received I g/day p. o. (33 to 83 mg/kg/day) for 8 weeks.Results were as follows:

Before After F'

HDL cholesterol, mm 0.83 0,05 (.02 0.09 <0.02

HDL cholesterotilotal cholesterol, soot 0.16 0,016 0.2 0.025 <0.02LDL cholesterol, ,,ssa 2.52 0,11 2.01 ((.19 <0.05Triglycerides, ma, 2.605 0.52 1.99 0.38 <0.02HDL triglycerides, ess, 0.28 0.06 0.395 0.036 NSHDL Phospholip., ,ssa. 1.15 0.06 (.38 0.06 <0.05Apo A, Ug/dI 190 0.0 231 4 <0.05Total muscle L curnitine. s,,s,Iea/mp' 20.92 4 per/mg 36.9 1 6.6 per/mg prot.

Ingesta estimation obtained by dietetic inquiry in 4 patients showed nochange in 3 and an increase in 1, thereby validating the results. Noimprovement of the myocardial performance was observed by M-modeechocardiography after L-carnitine administration.

Effects of antidiuretic and sex hormones on papillary plasma flow in therat kidney. F. Bayle, L. Eloy, M. Trinh, J. Grunfeld, and L. Bankir.INSERM U-90, Hôpital Necker, Paris, France. Papillary plasma flow(PPF) was measured by the albumin accumulation technique. Theamount of '251-labeled albumin found in the renal papilla after a 15-seciv. infusion is proportional to PPF. Homozygous Brattleboro rats withhereditary diabetes insipidus (DI) completely lack antidiuretic hormone

(ADH). In these rats we found significantly higher PPF than in controlheterozygous rats (HZ) (see Table). Acute (30 mm) arginine vasopressin(AVP) (TI) or dDAVP (T2) infusion decreased PPF in DI rats (dDAVPis a nonpressor analog of AVP with prolonged antidiuretic activity).Chronic (5 days) dDAVP administration (i.p. Alzet minipumps) (T3)further decreased PPF to control values. A significant correlation wasobserved between PPF and urine osmolality (Uosm). The above experi-ments were carried out on male rats. In subsequent experiments,performed in Wistar rats, we observed a significant difference in PPFbetween males and females, accompanied by a difference in Uoom.Females (F) had higher PPF and lower Uosm than males (M). Forty-eight-hour water deprivation (WD) increased Uosm to similar levels inM and F. PPF in females, although significantly decreased, did notdecrease to the values observed in normal or WD males. These resultsshow that antidiuretic hormone and/or its effects on papillary osmolalityinfluence the plasma flow rate of the renal papilla. Sex hormones alsoinfluence PPF since values observed in Wistar females remained higherthan those observed in males even when rats of both sexes reachedsimilar urine osmolality after water deprivation.

PPF UosmN p.1/mm g m0sm/kg H20

HZ 10 263 28 1877 70DI 8 446 310 248 23DI + TI 9 332 400 640 590DI + T2 6 375 29 702 68°DI + T3 6 262 40° 1745 73°M 8 240 23 1925 (N = 2)F 8 503 19b 1529 116M WD 6 255 28 2406 107°FWD 6 349± 11ab 2516± 108°

ap < 0.05 or less, DI vs. HZ or treated DI vs. nontreated DI or WDvs. non-WD of same sex; bF vs. M or F WD vs. M WD.

Dimeric structure of IgA in mesangial deposits in Berger's disease. M.C. Bene, G. Faure, and J. Duheille. Faculté de Médecine de Nancy,Vandoeuvre, France. Dimeric IgA elaborated in mucosae present twospecific characteristics: they possess a J chain (for joining piece) andare able to bind the secretory component (SC) secreted by the epitheli-urn. Twenty cases of Berger's disease were found with these twoproperties of mesangial deposited IgA. This study was performed byimmunofluorescence on frozen-cut kidney sections. Two methods wereused: (1) J chain was visualized by indirect immunofluorescence with anantiserum of controlled specificity; (2) SC was prepared from humancolostrum with isolation, purification, and control done by immunodif-fusion. This free SC was incubated in vitro with the kidney sections for1 hour in a moist chamber. Its specific binding by mesangial IgA wasascertained by direct immunofluorescence using an anti-SC antiserumadsorbed with monomeric aggregated IgA, the specificity of which hadbeen controlled. A double labeling IgA/SC with antisera (anti heavychain and SC) rhodamin- and fluorescein-conjugated, respectively,confirmed the localization of these two components. These tests werepositive for the 20 cases studied. It appears therefore, that the charac-teristic mesangial deposits in Berger's disease are composed of dimericIgA of mucosal and not systemic origin.

426

Kidney International, Vol. 20 (1981), pp. 426—433

AbstractsFrench Society of Nephrology

Paris, FranceJanuary 29, 1981

Abstracts 427

Factor XII deposition in extramembranous glomerulonephritis. J.Berger, H. Yaneva, and F. Josso. Hôpital Necker, Paris, France.Hageman factor has been demonstrated by immunofluorescence in 12out of 23 cases of extramembranous glomerulonephritis (membranousnephropathy). Factor XII was deposited, together with LgG, on theouter aspect of the glomerular basement membrane. Prekallikrein wasassociated with factor XII in every case. No factor XLI was found in 200renal biopsies from patients with other renal diseases, including thevarious other forms of glomerulonephritis. Specificity of antifactor XIIserum was controlled by inhibition of functional factor XII activity ofnormal plasma and by double immunodiffusion against normal plasmaand factor-X1I-deficient plasma. The demonstration of factor XII inmembranous nephropathy is rather unexpected since neither antigen-antibody complexes nor aggregated immunoglobulins seem to fix thisfactor. It is possible to imagine that renal vein thrombosis associatedwith membranous nephropathy might be related to factor XII activationand that kinins generated by kallikrein might be involved in changes inglomerular permselectivity.

Parathyroid carcinoma, adenoma, hyperplasia associated in a patientwith chronic renal insufficiency on dialysis. Y. Ber/and, M. Olmer, U.Lebreuil, I. Grisoli. Service de néphrologie, Hôpita/ de Ia Conception,Marseille, Service d'anatomopathologie, Hôpital Nord, Service dechirurgie générale et endocrinienne, Hôpital de Ia Timone, Marseille,France. A 62-year-old female patient with renal polycystic disease andchronic renal insufficiency, requiring dialysis during the past 3 years,presented with diffuse bone pain, predominantly lumbar and lassitude.Radiologic studies showed diffuse osteoporosis and destruction of the4th lumbar vertebra. Calcium levels were normal (2.30 to 2.50 mmoles)with increased PTH levels (1820 l-EqIml). The presence of a cervicalmass led to the diagnosis of hyperparathyroidism. A cervicotomy wasperformed with ablation of four parathyroid glands and autotransplanta-tion of a portion of the left inferior gland on the arm. Pathology studiesshowed the existence of carcinomas in the right superior and inferiorglands, adenoma of the left superior gland, and hyperplasia of the leftinferior gland. The association hyperplasia-adenoma-carcinoma couldbe explained by an initial hyperplasia of the four glands due to renalinsufficiency, transformation of three in adenomas, two of whichbecame carcinomas. The patient's status was significantly improvedfollowing surgery.

Effects of uremic middle molecules on auricular fragments of embryon-ic heart. P. Bernard, J. Rinaudo, M. Crest, J. Moret, A. Crevat, P.Galice, N. Fournier, A. Murisasco, S. Saingra, and R. Frayssinet.Laboratoire de Biophysique Cellulaire, Faculté de Médecine Nord,Marseille, France. We present the results obtained on auricular frag-ments of embryonic chick hearts with plasma ultrafiltrates directlyobtained from uremic patients treated by hemodialysis, uremic middlemolecules separated from plasma ultraffitrates of the same patients(peaks 7, 7c, and 7 d—e), and middle molecules separated from urine of anormal subject (peak 7). Various effects were obtained according to theconcentration of the middle molecule fraction used: tachycardia, brady-cardia, cardia arrest. All these effects were reversible by washing innormal medium. Sodium chloride solutions of the same osmolarity werewithout effect, so a simple osmotic effect was eliminated. Moreover,peak 7 d—e was inactive. So we eliminated an artefact due to thereagents and separation techniques.

Lipoprotein disorders in chronic ambulatory peritoneal dialysis. P.Bones, A. Slingeneyer, M. L. Solera, M. Ringenbach, J. S. De Graeve,H. Ton That, P. Valdiguie, C. Mion, J. M. Suc. Service de Nephrologieet de Biochimie, Groupe INSERM U 133, Toulouse, et Service deNephrologie, Montpellier, France. This study was carried out on twogroups: group I, normal healthy volunteers (N = 10; age, 75.1 7.4)without any cardiovascular disease or chronic renal failure; group 2,patients with end-stage renal failure undergoing chronic ambulatoryperitoneal dialysis (CAPD) )N = 13; age, 68.5 5.6). These patientswere given a 1700-cal, 2-g/kg protein diet. We studied serum lipids,glucose, and insulin levels in comparison with the control group. Ourresults are as follows: fasting glucose was within the normal range,plasma insulin, level was significantly higher (P < 0.01), total cholester-ol was increased (P < 0.05), VLDL cholesterol was increased (P <0.01), and HDL cholesterol was decreased (P < 0.05) with an increased

ratio (VLDL cholesterol + LDL cholesterol)/HDL cholesterol (P <0.01), increased total triglycerides (P < 0.05), VLDL triglycerides (p <0.05) and HDL cholesterol/HDL triglycerides ratio (P < 0.05). Thelipoprotein abnormalities are similar to type IV hyperlipemia and mightbe induced by changes in carbohydrate metabolism. The increased(LDL cholesterol + VLDL cholesterol)/HDL cholesterol ratio mightplay a role as an atherosclerosis rask factor in these patients undergoingCAPD. When compared with lipid abnormalities in a group of patientson hemodialysis (N = 17; age, 54.4 14), the abnormalities in uremicpatients on CAPD appear to be higher, namely increased VLDLcholesterol and VLDL triglyceride and an increased total CH/HDL CHratio.

Low level of antithrombin III and plasma antithrombin activity innephrotic syndrome. F. Bouissou, B. Boneu, M. Abbal, P. Sie, C.Caranobe, and P. Barthe. C.H.U. Purpan, Toulouse, France. It hasbeen suggested that thrombosis, a major complication in the nephroticsyndrome (NS), was related to low concentration of antithrombin III(ATIII). We studied 28 children with idiopathic NS and determined theplasma antithrombin activity according to the technique of Howie, theATIII by electro immunodiffusion, the a2 macroglobulin (a2M) and alantitrypsin (aAT) by radial immunodiffusion. We compared the resultswith normal children and adults. In NS, the decrease of ATIII andaIAT, by urinary loss, is correlated with hypoalbuminemia; however,when compared to controls, plasma antithrombin activity is higherbecause of the increase of the a2M (negative correlation with ATIII andserum albumin). In spite of the dramatic reduction of ATIII in 15children, no thromboembolic complication occurred. These resultssuggest that in NS the determination of ATIII alone has no value topredict thrombotic risk, whose pathophysiology seems more complex.Heparin in these patients is not effective and could be dangerousbecause of inhibition of ct2M antithrombin activity.

High frequency of HLA-DR-7 in children with idiopathic nephroticsyndrome: Correlation with allergic status. F. Bouissou, A. De Mouzon,P. Barthe, and E. Ohayon. CHU Purpan, Toulouse, France. Idiopathicnephrotic syndrome (INS) is likely to be underlied by immunologicmechanisms with special incidence of atopic symptoms. In thesepatients with atopy, an increased frequency of HLA-BI2 was found.Because there is no data on HLA-DR typing on this subject, it is the aimof this work. Fifty-four children with INS (mean age, 8.1 3.5 yr) werestudied. HLA-A and =B typing was performed by the NIH standardmicrolymphocytotoxicity technique, and HLA-DR by double fluores-cence. The results were compared to 49 children with various glomeru-lonephritis (mean age, 11.1 3.6yr) and 91 healthy blood donors of thesame area. Allergic status was defined by clinical, biological (IgE), andskin tests criteria. No significant deviation was found for HLA-A and=B antigens in the three groups studied and between patients with andwithout allergic status. High DR-7 frequency was found in INS (67% vs.31%; relative risk, 4.4; P = 2.4 10-i). No obvious correlation could bedemonstrated between HLA-DR-7 and steroid responsiveness, clinicaloutcome, and histologic studies. When these patients are dividedaccording to allergic status, HLA-DR-7 frequency was 92% (22/24) inpatients with allergy vs. 44% (11/25) in nonallergic INS (relative risk,14; P = 0.00037). These results suggest that INS could be an immuno-logic disorder who pathogenesis is related to the major histocompatibil-ity complex-linked immune response gene near DR-7.

Factors of risk of aseptic bone necrosis in renal transplant patients. G.Bouteiller, F. Dehais-Goffinet, D. Durand, H. Ton-That, and J. M.Suc. Service de Nephrologie, CHU Rangueil, Toulouse, France.Osteonecrosis (ON) in renal transplant recipients is still a disease inwhich the factors of risk are unknown. The aim of the present study wasto determine which of clinical, biological, and radiological data could beused as possible predictors of osteonecrosis. Some parameters ap-peared as no value to characterize the group of ON patients: age, sex,time on dialysis, phosphoremia, alkaline phosphatase, cholesterolemia,cumulative dose of corticosteroids. However, a multifactorial analysisperformed with a computer on 49 patients (19 of them had ON) showedthat it was possible to evaluate the risk of ON through the followingformula: number of transplant rejections treated by corticosteroids +mean overweight during the first 6 months after transplantation +hyperparathyroidism assessed on radiologic criteria — mean calcemia in

428 Abstracts

the first month following transplantation R. According to a scoreobtained by positive or negative points for each parameter, the higher isR, the greater the risk of ON. Thus, among 21 patients with R 0,none has ON. In contrast, the 9 patients with ON are found among the28 others with R 1. As no multifactorial analysis has been so farpublished in this regard, our results need to be confirmed. Neverthe-less, it suggests that ON might be a multifactorial disease, as the resultof the conjunction of various metabolic abnormalities.

Continuous ambulatory peritoneal dialysis: Two years' experience. B.Canaud, A. Slingeneyer, and C. Mion. Dept. Nephrology, C.H.U.Montpellier, France. Since Sept. 1978, 94 patients (51 males, 43females) were treated by continuous ambulatory peritoneal dialysis(CAPD) using the following technique: (1) dialysate in 2-liter plasticbags with a luer connector; (2) a bacteriologic filter on the connectingline; (3) dialysate containing 15, 25, or 40 g of dextrose and 130 or 140mmoles/liter sodium. There were 3- to 5-bag exchanges per day. Thecumulative treatment duration was 59.6 patient years (mean/patient: 7.6months). Residual creatinine clearance was 2.0 0.7 mI/mm. Thirty-one patients started their maintenance therapy by CAPD; 45 hadprevious intermittent PD (IPD) and 8 previous hemodialysis (HD). Anexcellent blood pressure (BP) control was obtained in all patients.Orthostatic hypotension, observed in 16 patients during the first monthon CAPD, improved in 9 patients with the use of 140 mmoles/litersodium dialysate, but persisted in 7 patients (BP < 90/60 mm Hg).Refractory edema was observed in 18 patients. In 38 patients treated for6 months or more by CAPD, biological results were (means SEM):creatinine, 103 7 mg/liter; urea, 1.1 0.1 g/liter; total proteins, 64.82.6 g/liter; serum albumin, 32 2 g/liter; triglycerides, 3.9 0.7 g/liter;hemoglobin (Hb), 11.7 0.5 g/dl. Thirty-seven peritonitis episodeswere observed; 4 were associated to an acute visceral disease; theoverall peritonitis incidence was I episode every 19.6 patient treatmentmonths. In September 1980, 48 patients were still on CAPD, 22 hadbeen transferred to IPD and 6 to HD; 18 patients had died. These resultsconfirm the value of CAPD as a long-term treatment of end-stage renaldisease, Besides its role in maintaining an equilibrium state, CAPDobtains a good BP control without drug and an increase in Hb in mostcases. With the use of a bacteriologic filter, the peritonitis incidence ismaintained at an acceptable level. However, the high number oftransfers from CAPD to HD and/or IPD suggests that CAPD must be apart of a program integrating all modes of end-stage renal diseasetherapy.

Combination of a membranoproliferative glomerulonephritis with abenign monoclonal gammopathy: Report of two cases. P. L. Caraman,M. Kessler, F. Maurice, C. Huriet, G. Rauber and J. Duheille. CentreHospitalier Regional, Nancy, France. We report two cases of mem-branoproliferative glomerulonephritis with a lobular tendency associat-ed with a benign gammopathy gamma-2 lambda-2. The first patient, a5 I-year-old woman, shows a nephrotic syndrome, positive circulatingimmune complexes, a normal level of total complement and of compo-nents C3 and C4. The second patient, a 50-year-old male, shows aperipheral vascular disease associated with a type I cyroglobulinemiasimilar in composition to the circulating monoclonal immunoglobulin;he has a nephrotic syndrome with severe renal failure requiringhemodialysis. The peripheral vascular disease is improved by theplasma exchanges. Total complement and C3 levels are normal; thereare no circulating immune complexes. Immunofluorescent analysis ofthe renal biopsy in the two patients discloses thin endomembranousdeposits of C3 and, above all, thick deposits of C9 at the level ofglomerular and tubular basement membranes. The benign nature of thetwo gammopathies is based on the normal myelogram and the normallevel of plasma immuoglobulins with a followup of 2 years for the firstpatient and 1 year for the second one.

A scanning electron microscope study of renal vasculature of the rat oncorrosion casts. D. Case/las, A. Mimran, M. DuPont, and B. foyer.Med.D, CHR Saint-Charles, Montpellier, France. To gain additionalinformation on the existence of arterial shunts in renal vasculature, weused microsphere injection into the artery of a perfused kidney prepara-tion combined with corrosion-replication of arterial vasculature (Bat-son's resin). Use of this technique afforded the advantages of both rapidlight microscopic detection of shunts and of high three-dimensional

resolution by the scanning electron microscope. Our results clearlydemonstrate the existence of arterial pathways bypassing glomerulithroughout the renal cortex with increasing frequency from the superfi-cial to the juxtamedullary cortex. However, quantitative analysisindicated an absence of age-dependency in the latter area. In rats fromweaning to more than a year old, approximately 10% (range, 4 to 22%)of juxtamedullary glomeruli were bypassed by aglomerular vessels orglomerular shunts. From results of microsphere studies it may beconcluded that aglomerular circulation plays a negligible hemodynamicrole in the basal condition. However, its significance in abnormalconditions cannot be ruled out.

T Lymphocyte functions in mercuric chloride-induced membranousglomerulonephritis in man: Evidence for a defect of presentation of thehistocompatibility class II molecules at the cell surface. B. Charpentier,N. Faux, G. Manigand, D. Fries. Service de Néphrologie et Service deMédecine Interne, Hopital Paul Brousse, Villejuif, France. Membra-nous glomerulonephritis (MON) is one of the well-documented manifes-tations of autoimmunity during chronic mercuric chloride intoxication.We have carried out immunologic investigation of the T cell functions ina patient presenting mercuric-chloride-induced MGN. Circulating au-toantibodies and immune complexes were absent from the serum.Lymphocyte transformation with mercuric chloride over a wide rangeof doses (10-s to I0 st) was negative. E rosettes, mitogen reactivity,allogeneic reactivity evidenced by a one-way mixed lymphocyte culturegave normal results. These findings contrasted with severe impairmentof lymphocyte stimulation capacity. This defect could be related to theinability of D,DR products to be exposed at the cell surface, impedingthe allogeneic recognition by foreign lymphocytes. This lymphocytedefect in the course of mercuric chloride MGN in man would becorrelated with lymphocyte abnormalities found in experimental mercu-ric chloride-treated rats. In Brown Norway strain, mercuric chlorideintoxication leads to an autoimmune GN with abnormalities of Blymphocyte functions. This present study favors a direct role ofmercuric chloride on lymphocytes rather than a direct action on theglomerular basement membrane.

Treatment of 298 hypertensive patients by tienilic acid: A retrospectivestudy. M. Colliard, P. Tcherdakoff. Hópital Ambroise Pare, Boulogne,France. Two hundred ninety-eight hypertensive patients received tieni-lic acid (ticrynafen) as part of antihypertensive therapy. in 295 cases,this drug was associated with a potassium-sparing diuretic, and theaverage length of treatment was 24 months. Considering the wholegroup of patients, the average serum creatinine did not change signifi-cantly. A moderate rise in serum creatinine levels was noted in 17 casesbut cannot be specifically linked to the therapy in all certainty. Twohundred fifty-three cases were investigated systematically for serumtransaminase levels during treatment: serum levels were moderatelyelevated in 18 cases, but the relation between tienilic acid and this rise,although possible, cannot be proven in these patients. According to thepresent data, it seems that the danger of nephrotoxicity of associatingtienilic acid and potassium-sparing agents has been overestimated andthat such an association can be used. The danger of hepatotoxicity ofthe drug is real but the occurrence is rare and should be put in balancewith the danger of other antihypertensive drugs and of other hypourice-mic drugs such as allopurinol.

Blood kinetics and a-blocking effect of oxprenolol and its main conju-gated metabolite after a single oral dose in hemodialyzed patientS. P.Dayer, P. Glasson, A. Gorgia, L. Ba/ant, and J. Fabre. Department ofMedicine, University of Geneva, Switzerland. Oxprenolol (Ox) is arapidly metabolized f3-adrenoceptor blocking drug, widely used inuremic patients. The aim of this study was to establish: (1) the kineticsof Ox and its main metabolite, a glucuronide conjugate (Cm), in renalfailure, (2) the cardiac effect of Ox, Cm, or other metabolites retained inuremia, (3) the relevance of Cm as a reserve pool of Ox, as postulatedfor propranolol. The kinetics of Ox were studied on whole blood using agas-liquid chromatography; Cm blood levels were obtained as thedifference in Ox levels between 3-g1ucuronidase-hydro1yzed and non-hydrolyzed samples. The 3-blocking effect was measured by means ofthe reduction of exercise techycardia on a bicycle ergometer before, 3hr, 5 hr, and 9 hr after an oral dose of 40mg of Ox. Work load was set toreach a mean cardiac frequency of 135 beats/mm before medication. Six

Abstracts 429

hemodialyzed patients free of other disease or drug were studiedfasting. The results show that kinetics of Ox are not affected by renalfailure: blood concentration 1 hr after the dose was 316 (SD) 160 ng/ml; area under the blood concentration curves (AUC,t) was 670 277ng mt' hr; t'/2 was I 0.4 hr. Cm, on the contrary disappearedextremely slowly: t½ was 123 74 hr rage from 60 to 234 hr (a morethan tenfold increase with respect to normal subjects). In spite of theretention of Cm and other unmeasured hydrophilic metabolites, theduration of cardiac effect was short, comparable with the valuesobserved in normal subjects. During hemodialysis sessions Cm wascleared with a tV2 of 5.6 hr. Conclusion. (1) The kinetics of Ox are notaltered by renal failure but Cm elimination is markedly reduced. (2)There are no "clinically active" metabolites of Ox in man, as judged bythe lack of noticeable cardiac effect after a few hours. (3) Aftera single40 mg dose of Ox in anuric patients, the Cm pool does not seem to playa major role in the late effect of Ox. Therefore, Ox may be administeredto uremic patients without modification of the dosage regimen.

Leucopenia and disturbances in pulmonary gas exchange during hemo-dialysis with different types of membranes. W. De Backer, G. Verpooten,P. Vermeire, J. P. Van Waeleghem, H. Van Beek, L. Muyl/e, and M. E.De Broe Depts. of Nephrology, Hypertension and Pulmonary Medi-cine, University of Antwerp, Wilrijk, Belgium. A decrease in peripheralleukocyte count and arterial oxygen tension (aPo2) is frequently ob-served during the first hour of hemodialysis (HD). Intrapulmonaryleukostasis induced by activation of the complement system andsubsequent hypoxemia is the explanation given by a number of investi-gators. Others propose alveolar hypoventilation caused by loss ofcarbon dioxide through the hemodialyzer. We made a comparativestudy in 6 patients using three different types of hemodialyzers:cuprophane (CP), celluose-acetate (CA), and polyacrilonitryl (PAN). Atseveral time intervals, simultaneous measurements of total and differ-ential white cell count, blood gases, histamine and complement factorswere performed. During 7 HD sessions using CP and 4 HD sessionsusing PAN, ventilation studies were performed using mass spectrome-try to obtain direct measurement of the alveolar oxygen tension (aPo2)and the alveolar-arterial oxygen gradient (al-a-Do2). One hour after thestart of HD, hypoxemia was significantly more pronounced in HD usingCP compared to CA (P < 0.05) and PAN (P < 0.025). When theclearance rate of histamine is taken into account, it seems likely thatsignificant amounts of histamine were produced in HD with all mem-branes. Activation of the alternative pathway of the complementsystem was qualitatively demonstrated in some HD using CF. The al-a-Do2 was significantly increased during the first hour in HD Using CP (P<0.02) where as in HD using PAN no significant increase was found (P>0.05). In the same period, no significant decrease of aPo2 occurred (P> 0.05). From these data, we conclude that there is a marked differencein hypoxemia and leucopenia using different membranes. The increaseddirectly measured al-a-Do2 indicates that VIQ inequality is the mostlikely cause of hypoxemia during the first hour of HD. The role ofhistamine and complement activation in the genesis of uneven V/Q isstill speculative.

Acute nephrotoxicity of antibodies directed against a basement mem-brane proteoglycan. J. B. Foidart, J. M. Foidart, J. Hassell, C.Dechenne, and P. Mahieu. Department of Medicine, University ofLiege, Liege, Belgium, and Laboratory of Developmental Biology andAnomalies, N.J.D.R., N.i.H., Bethesda, Maryland, USA. The glomer-ular basement membrane (GBM) is composed of collagenous andnoncollagenous glycoproteins and of proteoglycans. A proteoglycancontaining heparan sulfate has been purified from the BM matrixsecreted by a murine tumor (EHS sarcoma). Antisera directed againstthis proteoglycan were obtained by immunization of rabbits with thepurified antigen mixed with complete Freund's adjuvant. Their specific-ity was demonstrated by indirect immunofluorescence performed onnormal rat kidney slices, and by cross-immunoabsorption. Their neph-rotoxicity was studied by injecting iv. 0.5 to 2 ml of antiserum intoSprague-Dawley rats weighing 200 to 250 g. The following wereobserved: (1) 80% of the animals developed proteinuria (20 to 50 mg/dl)1 hr after the injection; this proteinuria reached its maximum 1 hr laterand disappeared 2 hr later; (2) the proteinuna increased proportionallyto the volume of antiserum injected; (3) control rats receiving normalrabbit serum did not develop significant proteinuria; (4) all the kidneys

from rats injected with the antisera exhibited linear deposits of rabbitIgG along the GBM, whereas no rat C3 was detectable; (5) all the ratkidneys presented a mild and transient leukocyte proliferation; (6) thecolloidal iron staining of glomeruli was strongly decreased 1 hr after theinjection of antibodies, but returned to normal 2 hr later; (7) from invitro perfusion studies, it appeared that the proteinuria was notcomplement-dependent. These data demonstrate that antisera directedagainst this BM proteoglycan are nephrotoxic. They also suggest thatthis nephrotoxic activity may be related, in part, to a functionalalteration of some anionic sites of the GBM.

Fracturing bone disease in a hemodialysis patient probably related tooral aluminum ingestion. G. Fournier, J. L. Gaillard, R. Pourdon, andT. DrOeke. Service d'hemodialyse, Centre Hospitalier de Chartres,Laboratoire de Biochimie-Toxicologie, Hópital Fernand Widal, andDepartment de Nephrologie, Hôpital Necker, Paris, France. The caseof a hemodialysis patient is reported who suffered from spontaneousbone fractures with X-ray and bone microscopy evidence of osteomala-cia probably related to aluminum intoxication. Her elevated plasmaaluminum concentration (16.6 moles/Iiter) was not due to an increasein dialysate aluminum concentration but occurred via the oral routesince the patient had intestinal hyperabsorption of aluminum. Evidenceof increased intestinal absorption of the metal was provided by an oralaluminum overload (2 x 12 g of aluminum hydroxide administeredduring 48 hrs). An identical overload performed in two control hemodi-alysis patients with a much lower plasma aluminum concentration didnot induce such a hyperabsorption. The cause of the augmentedintestinal absorption of aluminum remains unknown. Conclusion: Thepossibility of an increased intestinal absorption of aluminum should beconsidered in each chronic hemodialysis patient with hyperaluminemia.

Effect of captopril on renin secretion by intact and denervated kidneysin the dog. J. P. Girolami, J. L. Ader, D. Durand, T. Tran Van, andJ.M. Suc. Laboratoire de Physiologie and INSERM U 133, CHU deRanqueil, 31062 Toulouse, France. Though RS is suppressed bychronic renal denervation, the effect of acute denervation and theresponsiveness of renin secreting cells have not been studied. Thus, weassessed these latter points by using a comparison between the reninsecretory responses of the denervated (DK) and of the controlateralintact kidney (1K) of dogs (N = 12) to inhibit angiotensin II formationproduced by the converting enzyme inhibitor captopril (1 mg/kg, i.v.).Renal hemodynamic and functional parameters were monitored 30 mmafter surgery for four consecutive periods. After unilateral denervation,sodium excretion (UNOV), fractional sodium excretion (FENa), andrenal blood flow (RBF) were greater by 134, 86, and 22%, respectively,while glomerular filtration rate (GFR) did not differ and RS rate waslowered by 40% when compared to the 1K. Captopril produced asignificant decrease in blood pressure (—24 5 mm Hg) and similarrelative increases in UNaV, FENa, and RBF above their respectivecontrols in both kidneys while GFR remained constant. In contrast,whereas RS rate in the 1K rose progressively after captopril (from 6331 before captopril to 308 241 ng/min 60 mm after captopril), the RSrate of the DK did not rise beyond an initial increase (from 37.5 21before to 107 78 ng/min 20 mm after) and remained significantlybelow those of the 1K at all time periods. Our results indicate that arelative refractoriness of the renin secreting mechanism occurs soonafter denervation. It possibly reflects the net effect of an increase in thetransmural pressure at the baroreceptor site, an increase in sodiumdelivery to the macula-densa and/or a reduction in direct neural input tothe renin secreting cells.

Renovascular hypertension in the elderly: Poor prognosis and progres-sion of the vascular lesions. R. Gonthier, J. C. Sabatier, J. Toulon, B.Laurent, C. Genin, C. Veyret, A. Gelet, J. Tostain, X. Barral, and F.Berthoux. CHR Saint-Etienne, France. We analyzed, retrospectively,12 patients, aged from 63 to 73 years, with renovascular hypertensiondue to atheromatous lesions either unilateral or bilateral (4 out of 12).Malignant or accelerated hypertension with multiple visceral involve-ment was frequent (8 out of 12). The stenoses of the proximal parts ofthe renal arteries were rapidly progressive, ending in complete throm-bosis in 8 cases. Five patients received only a medical treatment, but in2 GFR deteriorated and in two others blood pressure was poorlycontrolled. Five patients underwent renal surgery nephrectomy (2),

430 Abstracts

aortorenal bypass (2), and bypass plus nephrectomy (1); however 2recovered normal GFR, but 2 died in the postoperative period. Threepatients had selective embolization of the renal artery, but only one wasdefinitively improved and one was later nephrectomized. These dataemphasize how difficult is the therapy of renovascular hypertension inthe elderly.

Increase of the specific cs-glucosidase acting upon the disaccharide unitsof collagens and basement membranes in the kidney cortex of diabeticrats. A. Grochuiski, G. Hirbec, J. Peyroux, and M. Stern berg. Départe-ment de Biochimie, Faculté de Médecine Broussais, Paris, Laboratoirede Pharmacodynamie, Faculté de Pharmacie, Paris, and Laboratoired'Anatomie Pathologique, CHU Henri-Mondor, Creteil, France. Anovel a-glucosidase has been described which appears to be highlyspecific for the hydroxylysine-linked disaccharide units of basementmembranes and collagens. It was therefore of interest to find out howits activity varied in the diabetic kidney since a thickening and anincreased degree of hydroxylysine glycosylation in the GBM and anelevated specific glucosyltransferase activity in kidney cortex havebeen reported. Wistar male rats of 210 g were injected iv. with 55mg/kgof body of streptozotocin (Sigma) and sacrificed 19 weeks after theinjection. Mean blood glucose level was 58 3 vs. 7.8 0.1 mmoles/liter in normal nonfasting controls. Kidney cortex glucosyl-galactosyl-hydroxylysine glucohydrolase specific activity was significantly in-creased in the dialyzed diabetic kidney cortex homogenate (21.1 1,3vs. 11.4 1.2 nmoles/hr/mg protein; P < 0.001). This increase in thespecific ct-glucosidase contrasted with a decrease in the nonspecific a-glucosidase activity with para-nitrophenyl-a--glucoside as substrate(76.4 4.2 vs. 133 10 nmoles/hr/mg; P < 0.001). The nonspecific 3-galactosidase activity on paranitrophenyl-j3-D-galactoside was alsofound to be significantly decreased in the diabetic kidney cortexhomogenate (721 36 vs. 1100 80 nmoles/hr/mg; P < 0.01) aspreviously described by Fushimi and Tarui in the x 10,000g supernatantof kidney cortex homogenate. Specific 13-galactosidase activity ongalactosyl-hydroxylysine residues was found to be very low in normalkidney cortex and not significantly modified in the diabetic. Theselective increase of the a-glucosidase specific for the disaccharideunits was confirmed in the kidney cortex homogenate after 23 and 28weeks of diabetes and disappeared after a 3-week treatment by insulin.It was associated with a thickening of the GBM with nonhomogeneousdensification of the lamina densa. It might reflect an increased glucoseturnover in the kidney basement membranes consistent with theincreased specific glucosyl-transferase activity reported by Spiro andSpiro.

Epidemiologic survey of analgesic nephropathy in France. J. Guenel.Hôpif a! Saint-Jacques, Names. As in several other countries, epidemi-ologic data are not yet available in France concerning the frequency ofanalgesic nephropathy (AN). It is thought to be rare, however. SinceOctober 1979, we have undertaken a nationwide retrospective surveycovering 6 years. Thirty-nine Departments of Nephrology were consult-ed and 28 answered. A total of 206 cases of AN were recorded for anaverage of 34.3 cases per year. This number represents about 2% of thepatients with end-stage renal failure. During the same period, 30patients with AN started regular dialysis treatment in 13 centers, i.e.,about 2% of all new patients in dialysis. This rate is close to that given inthe annual statistical report of EDTA for Europe (2.5 a 3.5%) but lowerthan that of some countries: 10% in the USA, 17.5% in Switzerland,18% in Belgium, 20% in Australia. In France, distribution is unequalbetween areas. AN is more frequent in the north (3.36% of the cases ofchronic renal failure) than in the south (0.25%). This difference may beexplained by local habits of using freely available drugs as well as by thedifficulty of diagnosis owing to inaccurately defined criteria.

Blood flow of subcutaneous arteriovenous shunts in chronic hemodialy-sis patients: Atraumatic measurement by dye-dilution method. T. Haas,G. Dongradi, P. Rocha, J. C. Kahn, B. Baron, J. P. Fendler. PoissyHospital, France. Blood flows in 9 side-to-end arteriovenous fistulaeand 7 arteriovenous grafts were measured in 16 chronic hemodialysispatients. Dye injections were given into the efferent vessel of the shuntclose to the arterial anastomosis. Dye dilution was measured into theefferent vessel more than 5 cm distal to the injection site. Dye wasinjected instantaneously by a small needle (amounts between 1.25 and

2.5 mg injected in a volume of 0.5 to 1.0 ml). In the case of arteriove-nous fistulae, a thermographic study confirmed prior to the study theabsence of any collateral vein between the injection site and the samplesite. Blood was collected at a continuous flow rate of 23 mI/mm from the"arterial" line of a double-lumen hemodialysis needle and was rein-fused distal to the blood sample point through the "venous" line of thedouble-lumen needle. Such a needle permitted: (1) a continuous reinjec-tion of the blood to the patient, and (2) a dialysis session aftermeasurement without a new blood access. Blood flows measured werebetween 0.39 and 2.6 liters/mm (mean = 1.35 liters/mm). Morphologyand reproducibility of dilution curves were good in 15 cases. Theseresults suggested a homogeneous mixing of blood and tracer, and aninsignificant error related to the pulsatility of the flow and the shortduration of the dilution curves. An atraumatic dye-dilution methodpermits, except in all but rare cases, precise measurement of blood flowin s.c. arteriovenous shunts of chronic hemodialysis patients. Bloodaccess is similar to the blood access for dialysis. A sample of 25 ml ofblood for calibration of the dilution curves is the only disadvantage ofthis method.

Bartter's syndrome and extrarenal hyperprostaglandinism In a patientwith brain tumor. B. Hurault de Ligny, A. Baumelou, A. Hornych, D.Pierre and M. Legrain. The occurrence of seizures and episodes ofaphasia in a 39-year-old woman led to the discovery of a brain tumor. Ayear later, hypokalemia was evidenced. Brain CAT scan showed a leftparietal hypodense, clearly demarcated area. Histologic examination ofthe surgical biopsy from left prerolandic region showed glial proliferation compatible with the diagnosis of a grade I astrocytoma. Thepersistent hypokalemia in the range of 2 to 2.6 mmoles/liter wassymptomless. There was a marked kaliuresis (88 mmoles/24 hr). Plasmamagnesium was low (0.62 mmoles/liter). Search for diuretics in theblood and in the urine and for phenolphtalein in the stools werenegative. Supine plasma renin activity was increased (14 ng/ml/hr;normal value, 2 to 3 ng/ml/hr) and was stimulated in the upright position(35 ng/ml/hr). The same pattern was found for plasma aldosterone(supine 30 pg/mI; normal value, 0 to 25 pg/mI; upright, 190 pg/mI).Urinary prostaglandin excretion was also considerably increased: pros-taglandin E2 (PGE2), 1017 ng/24 hr (normal value, 183 22 ng/24 hr);PGF2, 1268 ng/24 hr (normal value, 441 80 ng/24 hr). These biologicabnormalities were corrected by indomethacin (3 mg/kg/day orally for 6days). The diagnosis of Bartter's syndrome was based on these clinicaland biological data. On account of the presence of the brain tumor, thesite of prostaglandin overproduction was sought by evaluation ofprostaglandin levels in multiple venous blood samples collected duringselective catheterization. Increased plasma PGE2, PGF2 , 6 -keto-PGF1 and TxB2 concentrations were found in all blool samples.Particularly high levels were observed in the left jugular vein andsuperior vena cava whereas increases were very slight in both renalveins. These results demonstrated the essentially extrarenal and possi-bly tumoral origin of the hyperprostaglandinism. They also point out thepossible association of Bartter' s syndrome and brain tumor.

Results of the controlled trail of Institut Pasteur hepatitis B vaccine in48 French hemodialysis units. P. Jungers, P. Guesry, A. M. Courouce,A. Laplanche, E. Benha,nou, B. Lacour, F. Degos, and J. Crosnier.Hôpita! Necker, Paris, France. Institut Pasteur Production vaccine wasprepared from plasma of chronic carriers of HB5Ag (ad and aysubtypes), negative for HBeAg, inactivated by 1/10,000 formaldehyde,with aluminum hydroxide as adjuvant. Each I-mI dose contained 5 igof HBsAg. The vaccine lot was tested on chimpanzees for safety andimmunogenicity. After informed consent and exclusion of subjectspositive for HBsAg, anti-HBc, or anti-HBs, 367 high-risk permanentstaff members of 48 French hemodialysis centers were enrolled in thetrial. These volunteers received randomly, double-blind, three s.c.injections of 1 ml of either vaccine or placebo, at monthly intervals andwere followed monthly during a one-year period. The incidence of side-effects did not significantly differ between vaccine (17%) and placebo(15%) groups. HBV infections were observed in 12.3% of placeborecipients distributed throughout the whole 12-month followup period,and in only 3.6% of the vaccine recipients (P < 0.005), none occurringafter the 63rd day following the first injection. An immune response,defined by anti-HBs titers 10 mIU/ml on at least 5 successivesamples, was obtained in 94% of vaccine recipients. Anti-HBs level was

Abstracts 431

2,433 1,077 mIU/ml (mean 2 SEM) 4 months after the 1st injection,and 904 231 mUl/mi 8 months later. Following the booster injection(given between the 14th and the 18th month), it reached 74,740 33,490mIU/ml, These results demonstrate the safety, immunogenicity, andefficacy of the Institut Pasteur hepatitis B vaccine.

Hematuria, red cell casts, and renal biopsy. A. Kahan, E. Ronco, L.Morel-Maroger, F. Mignon, M. Beaufils, A. Meyrier, and G. Richet.Service de Néphrologie, Hôpital Tenon, Paris, France. To test thevalue of the search for urinary red cell casts, we studied the relationbetween hematuria, proteinuria, casts, and renal histology. Red cellcasts were systematically and thoroughly searched for, on freshlycentrifuged urine, by phase-contrast microscopy, and also renal biop-sies. Results. Among 69 cases, 58 were glomerulonephritis and 11nonglomerular nephropathies; the latter had no hematuria or red cellcasts. The 58 cases of glomerulonephritis were classified according to:(a) the presence (+) or absence (—) of hematuria (H) and urinary redcell casts (C); (b) the presence or absence of cellular proliferation(diffuse or focal and segmental) or renal histology; (c) the number ofcases with red cell casts in tubules on renal biopsy which is inparenthesis.

Urinarysediment Histology

Proliferative

Non-proliferativeDiffuse

Focal andsegmental

H(+) C(+) 5(1) 0 0H (+) C (—) 8 12(6) 4(1)H(—) C(—) 2 0 27

In 7 cases, red cell casts were found on renal biopsies but not in theurine (1 amyloidosis and 6 focal and segmental glomerulonephritis: 4IgA and 2 angeitis). In 6 cases with hematuria without proteinuria,glomerulonephritis was proven by renal biopsy (2 diffuse proliferative, 3IgA, 1 nonproliferative). Conclusions. (1) We confirm that hematuria isgenerally associated with proliferative glomerulonephritis (86%; 25/29).In cases with proteinuria without hematuria, renal biopsy rarely demon-strates proliferative glomerulonephritis. Hematuria without proteinuriaoften reveals glomerulonephritis (6/29); (2) In 50% (6/12) of focal andsegmental glomerulonephritis, red cell casts were found on renal biopsybut not in the urine; (3) Urinary red cell casts were only found in diffuseproliferative glomerulonephritis; but their frequent absence in hema-turic glomerulonephritis (80% of proliferative and 62% of diffuseproliferative forms) considerably reduces the clinical value of thissearch.

Preservation of renal function by phosphorus restriction: A nonspecificeffect? D. Laouari, C. Kleinknecht, M. Broyer, and F. Mounier.INSERM U. 192, Hôpital des Enfants-Malades, Paris, France. Thedeterioration of renal function (RF) in experimental renal insufficiencymay be slowed by a devoid phosphorus diet or by a poor protein diet.The purpose of the study was to elucidate the respective role of thesetwo factors. Five groups of uremic rats were compared: three (A, B, C)were fed ad lib diets differing exclusively in their phosphorus contentwhich was 0.03%, 0.2%, and 0.5%; two (D, E) received the 0.2% and0.5% diets but were pairfed with A rats. A rats showed (1) a lower foodintakethanratsBandC(l3.5 18.5a growth arrest while weight gain after 3 months was 50 12 and 8820g in pairfed rats D and E (A vs. D orE, P < 0.05), and was 120 12and 150 log in B and C rats fed ad lib, (3) a hypophosphoremia (0.75

0.05 mmoles/liter) with hypercalcemia (3.50 0.06 inmoles/liter),which were less severe in B and D rats (calcium 3.0 0.1; phosphorus,1.1 0.09 mmoles/liter), whereas C and E rats had normal serumlevels. Renal function was stable in all rats A, D, and E. Their mortalitywas 20%, 20%, and 27% after 8 months, whereas mortality was 80% and90% in B and C rats. Phosphorus intake was lower in B rats than in Erats (1.18 0.04 vs. 2.53 0.22 mmoles/day during the first 3 months,P < 0.001). In conclusion, the deterioration of RF was much moreclosely related to food and protein intake than to phosphorus intake.However, since deaths occurred earlier in C rats than in B rats, a slighteffect of phosphorus, possibly mediated by the greater weight gain,cannot be excluded.

Strong association between HLA-DR4 and Berger's disease. P. LePogamp, D. Chevet, P. Simon, M. P. Ramée, M. Gueguen, R.Fauchet. Unite de Nephrologie, CHU Pontchaillou, Rennes, Servicede Néphrologie, C.H. La Bauchée, St Brieuc, Laboratoire d'Histocom-patibilité, C.T.S., Rennes, France. Conflicting results have been pub-lished concerning an association between Berger's disease and HLA-Aand -B antigens, especially Bw35 and B12. Forty-five consecutiveunrelated patients were therefore screened for HLA-A, -B, and -DRantigens. All the patients had mesangial IgA deposits and no associatedsystemic or liver disease. Controls for HLA-A and -B typing consistedof 356 and for HLA-DR typing of 114 locally recruited healthy blooddonors. No significant HLA-A or HLA-B antigen excess was found,whereas a slightly increased Bw35 antigen frequency was noted (28.9%vs. 12.9%, P < 0.14). But there was a highly significant increase in thefrequency of HLA-DR4 (48.9% vs. 19.5%, P < 10 — 3; R = 3.96) with asecondary association with Bw35 and A2-Bl2 antigen combination. Thepreliminary results of clinical correlations will be presented.

Anti-GBM crescentic glomerulonephritis and angioimmunoblasticlymphadenopathy. P. Le Pogamp, P. Y. Le Prise, M. P. Ramée, P.Mahieu, and D. Chevet. Unite de Néphrologie, CHU Pontchaillou,Rennes, Unite d'Hematologie, C.M.D., CHU Hôtel-Dieu, Rennes,France, and Inst itut de Medecine, HOpital de Bavière, Liege, Belgium.A 67-year-old patient developed simultaneously a glomerulopathy and alymphoproliferative disorder consisting of angioimmunoblastic lymph-adenopathy. Hematologic data was typical: generalized lymphadenopa-thy, hepatosplenomegaly, immunologic abnormalities, specific his-tologic picture. Despite high-dose corticosteroid therapy, glomerulo-pathy clinically worsened. A renal biopsy then performed disclosed acrescentic glomerulonephritis (75% of crescents), with linear depositsof IgG and C3 on immunofluorescence microscopy. The autoimmunemechanism of the glomerulonephritis was assessed by high titers ofserum anti-GBM antibodies in RIA. Combination of cytotoxic drugsand plasma exchanges induced a striking improvement of both syn-dromes.

Comparative effects of propranolol and atenolol in the control ofsecondary hyperparathyroidism of chronic renal failure. R. Makdassi, P.Moriniere, B. Coevoet, J. Guéris, C. Calmettes, Flouvat, A. Fournier.CHU Amiens, Hop. Lariboisiêre, St Antoine, et A. Pare, Paris,France. Propranolol (P), a 131 + 132 blocker, has been proposed as thetreatment of choice of hypertension in uremic patients because itsuppresses PTH secretion when given iv. In general practice 131betablockers are usually preferred because of various advantages.However, we have previously shown that metoprolol (a 31 blocker) wasunable to suppress PTH secretion when acutely administered in uremicpatients. The aim of this randomized crossover study was to comparethe chronic effects of 2 months of therapy with either P or Atenolol (A),another 131 blocker, when orally administered at equal antihypertensiveactivity, in 24 nondialyzed uremic hypertensive patients, on theirplasma levels of PTH (C and N terminal assays), calcitonine, 25 OH D,total calcium, phosphate, proteins, bicarbonate, urea, and creatinine.Plasma levels of A and P, measured to check compliance, were found inthe usual therapeutic range. No significant difference was found, exceptin plasma bicarbonate, which was higher with P (P < 0.05). It isconcluded that the long-term control of secondary hyperparathyroidismis comparable with A and P. However these results could be interpretedby an initially greater suppressive effect on PTH secretion with P, thispossibly leading to an increase of bicarbonate levels because ofincreased tubular reabsorption and to a secondary fall of ionizedcalcium with a subsequent rise of PTH secretion. This suppression ofPTH secretion, weaker with A than with P, is compatible with the invitro demonstration of 131 and 132 parathyroid receptors.

Effects of inclomethacin and possible role of prostaglandins on renalcalcium excretion. L. Monnier, L. Aguirre, C. Colette, and J. Mirouze.Clinique des Maladies Métaboliques, Hopital St Eloi, Montpellier,France. Prostaglandins (PG) act on the renal tubules, changing renalcyclic AMP content, and water and sodium excretion. We evaluated thepossible role of PG on renal calcium excretion in humans through thePG inhibitory effects of indomethacin. Methods. Renal calcium excre-tion was evaluated by a technique which gives a specific index oftubular calcium transport. After an i.v. bolus of 20 Ci of 47CaC12, the

432 Abstracts

time courses of radioactivity both in urine (R[tI) and in the glomerularultrafiltrate (l[tJ) were measured. The latter was calculated from thetotal plasma radioactivity after correction for the glomerular filtrationrate (GFR), and for the ionized plasma calcium. The time course, Ro(t),of the urinary radioactivity after a 47Ca bolus theoretically injecteddirectly into the glomerular filtration system was obtained by applyingan inverse convolution procedure to R(t) and 1(t). Several parameterswere derived from Ro(t): (1) the total fractional urinary calciumexcretion as percent of total dose (TFEca, %TD) (2) the peak excretionrate (Uca max, %TD), (3) the mean transit time (MTT, mm). Protocol.The aforementioned parameters were determined in 7 healthy subjectsin basal conditions and again after 10 days of treatment with 100 mg ofindomethacin daily. The results are summarized below

Before After indomethacin P

TFEca, %TD 5.02 0.57 8.18 0.97 <0.02Uca max, %TD/min 0.050 0.006 0.051 0.007 NSMYF, mm 1.35 0.27 1.77 0.23 NS

Indomethacin produced an increase in calcium excretion. As indometh-acm did not produce any significant change in GFR (125 7 mI/mmbefore vs. 129 9 after) one can assume that PG plays a role in tubularcalcium reabsorption. However the mechanism remains to be elucidat-ed: direct action or mediated through the cyclic AMP system.

Prospective study of gentamicin nephrotoxicity in the human kidney.G. Paulus, G. Verpooten, R. Rutsaert, P. Tulkens, F. Rods, andM. E.De Broe. Dept. Nephrology-Hypertension and Pathology, University ofAntwerp, Institute of Cellular and Molecular Pathology, UniversitéCatholique Louvain, MenselUke Anatomie, Vrije Universiteit Brussel,Belgium. A prospective comparative study of nephrotoxicity of amino-glycosides in the human kidney was made. The preliminary results ofthe early nephrotoxicity of gentamicin (G) are reported. Patients withrenal neoplasia partly involving the kidney either received G, 1.5 mg/kgt.i.d., during 4 days before surgical operation or served as controls. Infive patients treated with G, we made the following observations: Gaccumulates in the renal cortex. Renal function remained unaltered.Light microscopy showed no specific tubular lesions. Histochemistry ofthe brush border (alkaline phosphatase, y-glutamyl-transferase, leu-cine-aminopeptidase) was normal. Sphingomyelinase activity was nor-mal. Electron microscopy (EM) showed the presence of dense osmio-philic lamellar structures ("myeloid bodies"), generally occupying onlya limited area, within most of the lysosomes. The lysosomes wereidentified by the deposit of acid phosphatase reaction product (leadphosphate). G given at normal doses during 4 days induces earlylysosomal lesions similar to previously described lysosomal alterationsin patients with acute renal failure after prolonged G treatment. Theseearly lesions, however, were detected only by morphologic methods(EM).

Preventive hemodialysis in pregnant woman with advanced renalfailure and severe hypertension. K. Rebaiz, F. Lesdain, B. Pierrot, andC. Wolf Service de Medicine D, Orientation Nephrologique, et Servicede Gynecologie Obstetrique, Hôpital Manchester, Charleville-Me-zieres, France. A 27-year-old woman, mother of a 6-year-old child, wasreferred at the beginning of her second pregnancy for acute renal failure(ARF) due to chronic pyelonephritis with bilateral vesicoureteric re-flux. The creatinine clearance was IS mI/mm. The blood pressureremained high (160/110 mm Hg) despite powerful antihypertensivetherapy by acebutolol, 800 mg/day, dihydralazine, 75 mg/day, andclonidine 0.300 mg/day. The patient underwent PHD at the 24th week ofpregnancy to decrease the maternal and fetal risk. Hemodialysis (HD)(Rhodial-RP 6 system) was performed for 3 hours thrice a week with anarteriovenous fistula. Early during dialysis, she developed uterinecontractions which were suppressed by salbutamol (3 mg/day). Theobstetrical followup was done by serial ultrasound scanning, monitoringof fetal beats and amniocentesis. An hydramnios was present. Thedelivery by vaginal route occurred at the 34th week of gestation. Thel700-g male infant showed no congenital abnormality and had an Apgarscore of 9. HD was discontinued 2 months after delivery but it had to beresumed 12 months later. In this case, the benefits of preventive HDwere the control of hypertension (115/75 mm Hg) with a minimal

treatment (clonidine, 0.300 mg/day), the improvement of nutrition witha free diet and the suppression of acidosis. This case and the review ofthe literature demonstrate that the indications of preventive HD inpregnancy should be based on the diagnosis of the nephropathy, theseverity of renal failure, and the poor control of hypertension byantihypertensive drugs.

Evidence for the presence of antidiuretic and antinatriuretic factors inhuman cirrhotic ascites. M. Robin, P. Cambier, J. P. Godon, and A.Nizet. Inst it ut de Medicine, Département de Clinique et de Semeiologiemédicales, Université de Liege, Liege, Belgique. The factors involvedin the pathogenesis of cirrhotic ascites (CA) are numerous, but theirrelative influence is poorly known. The disappearance of a natriuretichormone was suggested as a possible cause. Our study was performedto investigate in alcoholic CA (N = 7) other factors suitable to explainthe salt and water retention. We used the administration of CA samplesin two bioassays: (1) totally isolated blood-perfused paired dog kidneys(N = 9) supplemented by ADH and DOCA, (2) cell-free perfused ratkidneys (N = 17). We used as control an artificial medium of the sameionic and oncotic concentration. The AC administration induced in thedog kidneys a strongly significant decrease (2 P <0.001) of diuresis andabsolute as well as fractional sodium excretion as compared to controls.In the rat system, we observed the same significant decrease (2 P <0.001) of water and sodium excretion after AC injection. In bothbioassays, no significant variation of RPF and GFR was observed.Conclusions. Our experiments were performed in conditions precludingthe involvement of an aldosterone or vasopressin increase on a natri-uretic hormone decrease. Thus, we have demonstrated in such patientsthe presence of at least one factor inducing water and sodium tubularreabsorption in two species. These factor(s) could play a role in thehydroionic retention observed in human cirrhotic ascites.

IgA nephritis in infectious mononucleosis. P. Simon, 0. Nouel, K. S.Ang, Y. Deugnier, and M. P. Ramée. Service de Néphrologie et Servicede Gastro-Enterologie, Centre Hospitalier La Beauchée, Saint-B rieuc,et Service d'Anatomie Pat hologique, C.H. U. de Pontchaillou, Rennes,France. A 17-year-old girl developed macroscopic hematuria duringinfectious mononucleosis (acute pharyngitis, cervical lymphadeno-pathy, splenomegaly, urticarial rash, anicteric hepatitis). The PaulBunnell test was negative, and 1gM antibodies to EB-viral capsideantigens (IgM-VCA) were positive to 1/640. Liver biopsy studied bylight and electron microscopy showed lesions compatible with infec-tious mononucleosis. Renal biopsy showed, by light microscopy, mildfocal and segmental glomerulonephritis; by electron microscopy, smallsubendothelial dense deposits; and by direct immunofluorescence stain-ing, granular deposits of IgA, 1gM, and fibrin along the peripheral loops.More effort should be directed to studying the role of Epstein Barr virusin young adults with IgA nephritis.

Porphyria cutanea tarda-like dermatosis in hemodialyzed patients: Tencases. F. Schillinger, J. M. Chalopin, C. Corbin, R. Montagnac, B.Perrier, S. Corbin, E. Jusirabo, G. Rifle. Service de Nephrologie, CHGTroyes, Centre Medico-Chirurgical de Chaumont-le Bois, Service deNephrologie et Reanimation Melabolique, CHU Dijon, France. Among250 patients on maintenance hemodialysis in three centers, 10 patients(2 females, 8 males), with an age range of2l to 63 years (mean, 44 years)developed porphyria cutanea tarda-like syndrome, 2 to 72 months afterinitiating hemodialysis treatment (mean, 19 months). Bullous lesionswere located on sunlight-exposed areas. They looked like those causedby porphyria cutanea tarda (PCT) in every aspect. Their course wasmostly characterized by attacks during the summer. Five patients hadonly one attack, two had 2, and one had 4 during four followingsummers. However, in two patients, the skin lesions were permanent,increasing in the summertime. Nine out of ten patients also showedincreased cutaneous fragility in response to trauma, and three had milia.One patient was successfully transplanted during 16 months: the skinlesions decreased but did not disappear. In every case, coproporphyrinor uroporphyrin levels in red cells, and urine and stool specimens werenormal. Under light-microscopic examination (six patients), the skinlesions were indistinguishable from PCT. Immunofluorescence studieswere carried out in four cases: IgG granular deposits were noticed at thedermoepidermaljunction in one case. The pathogenesis of this dermato-sis, of which about 50 cases have been reported, remains unknown. Alinkage had been suggested between this syndrome and HLA-B-l2:

Abstracts 433

HLA typing revealed the presence of this antigen in two out of sixpatients studied. In our series, we have found no obvious relation withinitial disease, the dialysers used, the quality of water, or the adminis-tration of drugs. Seven of these ten patients were being treated withfurosemide during their attacks. The plasma aluminum concentration ofthese patients was not different from the other hemodialyzed patients ofthe same centers. A possible tissue accumulation of this metal, particu-larly regarding the liver, cannot be eliminated; no liver biopsy wasmade. On the contrary, nine of ten patients have minor hepaticabnormalities: presence of the HBs Ag in seven cases and in four casesexcessive alcohol consumption. Moreover, transient increases in theserum transaminase levels occurred in five cases at the time of attacks.From a therapeutic point of view, two patients improved after oraladministration of carotenoids, 2.5 mg/kg/day.

Home peritoneal dialysis, long-term treatment of end-stage renaldisease patients with insulin-dependent diabetes mellitus: Five years'experience. A. Slingeneyer, J. L. Selam, C. Mion. Dept. Nephrology,University Hospital, Montpellier, France. From September 1975 toSeptember 1980, 16 patients with insulin-dependent diabetes mellitus(IDD) (mean age, 34.2 5.8 years) entered our home peritoneal dialysis(HPD) program. At start of treatment, residual creatinine clearance(Ccr) was (mean SD): 6.7 3.2 mI/mm. All patients had intermittentPD (IPD) three times a week with 120 to 150 liters of dialysate per week,for a cumulative treatment duration of 35.5 patient years; 7 patientswere transferred to continuous ambulatory peritoneal dialysis (CAPD)(cumulative treatment duration, 6.4 patient years). Insulin was givens.c. in 14 patients and i.p. in 2 CAPD patients. During the first week oftreatment, a 10.8% mean body weight loss, due to fluid removal, wasobserved: it was associated with a significant decrease of Ccr, whichwas I 0.8 mI/mn at the end of the first year. In 50% of the patients,long-term blood pressure control was difficult to maintain due tosymptomatic orthostatic hypotension. In 8 patients, diabetes controlwas poor according to Schlichtkrull M-value; HbA1 was 11.2 2,2%(normal, 5 to 8.5%). Biochemistries were (in g/liter): urea, 1.4 0.4;triglycerides, 2.6 0.7; total proteins, 66 6.1; albumin, 36.5 7.6;creatinine, 13.0 3.4 mgldl; haematocrit, 37.3 9.6%. There were fewinfections: 2 peritonitis episodes (PE) in IPD (1 PE every 17.2 patienttreatment years) and 3 PE in CAPD (I PE every 20.8 patient treatmentmonths). Five of 13 patients with neuropathy at start of treatmentimproved and 2 deteriorated. Vision improved in 5 patients anddecreased in 1; amputation was not required in any patient. There wasonly one death due to peritonitis associated to acute appendicitis after34 months of IPD. The actuarial survival rate was 89% at 3 years. Theseresults suggest that PD offers a good therapeutic alternative to theinsulin-dependent diabetic with ESRD: both a low incidence of peritoni-tis and no acceleration in degenerative vascular disease contributes to ahigh actuarial survival rate.

Anemia and aluminum intoxication: An experimental study in rats. M.Touam, F. Martinez, B. Lacour, and T. Drdeke. INSERM U.90 andNephrology Department, Necker Hospital, Paris, France. In aluminum(Al) intoxicated hemodialysis patients, a microcytic anemia has beenrecently observed. The part that Al could play in the pathogenesis oftheir anemia remains, however, hypothetical. We have allocated twogroups of 10 normal rats, respectively, to daily peritoneal injections ofeither a solution of aluminum sulfate (710 i.g of elemental Al) or thevehicle solution. Blood samples were taken 2 and 3 months afterstarting this treatment. After 2 months of Al intoxication versus vehicleinjection, a significant decrease was observed in hematocrit (13 0.8vs. 29 0.8%), RBC count (2.3 0.15 vs. 5.1 0.14 x 106/mm3), andhemoglobin (12.6 0.3 vs. 15.6 0.2 g/dl). After 3 months oftreatment, these differences between both groups were even more

pronounced. Moreover, the anemia of Al-intoxicated rats then becamemicrocytic (MCV, 52.7 0.3 vs. 56.3 0.3 3), strikingly hyperchro-mic (MCHC, 134 7 vs. 52 2 ig%), and hyporegenerative. Theirserum iron concentration was significantly lower than that of controls(18 1.1 vs. 29 1.3 i.moles/Iiter). Conclusion. Heavy aluminumintoxication in normal rats induces a microcytic and hyporegenerative,profound anemia which cannot be explained by a concomitant moderateiron deficiency alone. This anemia is unexpectedly hyperchromic. Thelatter was not observed in our hemodialysis patients with severealuminum intoxication whose anemia was microcytic and normochro-mic.

Wegener granulomatosis: A survey of three cases. 0. Toupance, J. P.Melin, S. Lavaud, C. Beranger, P. Birembaut, J. P. Brunois, and J.Chanard. Service de Néphrologie et Laboratoire Pol Bouin, C.H. U.Reims, France. Three male patients, 41, 50, and 56 years old, havingWegener granulomatosis were treated for 7 to 19 months. The initialpicture of the disease included the following localizations: 3/3 lungs, 2/3upper respiratory tract, 2/3 necrotic purpura, 2/3 kidneys with subacuteglomerulonephritis. Therapy was started with prednisone (1.5 mg/kg/day) and azathioprine (2.5 mg/kg/day) in one patient and with predni-sone, cyclophosphamide (2.5 mg/kg/day) and plasma exchange in thetwo others. Remission was obtained in the first months of therapy.Renal function returned toward normal in one and renal insufficiencywas maintained in plateau in the other. After 6 months on azathioprine,hematologic toxicity occurred, the dose was decreased, resulting in afatal relapse. After 6 months on cyclophosphamide, the patient withoutrenal involvement stopped the drug while maintaining prednisone.Subacute glomerulonephritis requiring hemodialysis occurred 2 monthslater, and improvement of renal function (creatinine clearance increas-ing from 5 to 30 mI/mm) was achieved in reintroducing cyclophospha-mide and plasma exchanges. The third patient still on cyclophospha-mide (1.5 mg/kg/day) is doing well after 19 months. From this study itappears that (1) cyclophosphamide (1.5 to 2 mg/kg/day) in associationwith prednisone, as proposed by Fauci, is the most suitable therapy ofWegener granulomatosis and (2) plasma exchange seems to have abeneficial effect at the start of therapy.

Role of renal vasoconstriction in the pathogenesis of mercuric-chloride-induced renal failure. R. Vanholder, J. Verbanck, S. Ringoir, and N.Lameire. Renal Division, Department of Internal Medicine, UniversityHospital, De Pintelaan, Belgium. Acute toxic renal failure was inducedin dogs by the i.v. bolus injection of HgCl2 at a dose of 3 mg/kg. Withina 3-hour period, an almost parallel decrease in glomerular filtration rate(GFR) and renal plasma flow (RPF) by more than 40% and an increasein urinary volume and urinary sodium excretion were observed. Renalvasoconstriction was then adequately prevented in this model by theadministration of the plasma volume expander Haemaccel® alone or incombination with the alpha-blocker phentolamine. Despite stabilizationof RPF, GFR in the Haemaccel0-phentolamine group fell at the samerate as in the unpretreated HgCI2 dogs. In the Haemaccel® group, RPFremained constant, and GFR, 3 hours after HgCI2 administration,decreased by only 18% compared to the control GFR value. The lesspronounced fall in GFR appeared essentially due to a rise in GFR bymore than 10% after Haemaccel® before the HgCI2 was administered.Comparison of the GFR with the experimental pre-HgCI2 volume-expanded GFR revealed a similar procentual fall as in the unpretreatedanimals. Finally, in both volume-expanded groups, urine and electro-lyte losses were more pronounced than after HgCl2 alone. It isconcluded that renal vasoconstrmction apparently occurs concomitantlywith a fall in GFR in the early stage of HgCI2-induced ARF. However,these changes in renal hemodynamics do not play an important pathoge-netic role in the generation of the ARF in this model.